Incyte Presents Positive Phase 1/2 Data for Latarcibart in Von Willebrand Disease, Supporting Ongoing Phase 3 Development
Incyte has announced comprehensive safety and efficacy results from its Phase 1/2 multidose clinical study evaluating VGA039 (latarcibart), an investigational monoclonal antibody designed to treat patients with von Willebrand disease (VWD). The complete dataset, which includes all 16 participants enrolled in the trial, was presented during an oral session at the 34th Congress of the International Society on Thrombosis and Haemostasis (ISTH 2026) in Paris.
The findings demonstrated substantial reductions in bleeding episodes across multiple forms of von Willebrand disease while maintaining a favorable safety profile. According to the company, the results further strengthen the clinical evidence supporting latarcibart as a potential prophylactic treatment capable of providing long-term bleed protection with the convenience of once-monthly subcutaneous administration.
Latarcibart is currently being evaluated in the pivotal Phase 3 VIVID-6 clinical trial, where researchers are investigating its potential to become the first once-monthly subcutaneous preventive therapy for patients with von Willebrand disease. If approved, the treatment could offer a significant alternative to the frequent intravenous replacement therapies that currently represent the standard prophylactic approach for many patients living with the inherited bleeding disorder.
Addressing an Unmet Need in Von Willebrand Disease
Von Willebrand disease is the most common inherited bleeding disorder, affecting millions of individuals worldwide. The condition results from deficiencies or functional abnormalities of von Willebrand factor (VWF), a protein that plays an essential role in blood clotting by helping platelets adhere to damaged blood vessels and stabilizing clotting factor VIII.
Patients with VWD experience a wide spectrum of bleeding symptoms, ranging from frequent nosebleeds and easy bruising to heavy menstrual bleeding, gastrointestinal hemorrhage, prolonged bleeding after surgery or dental procedures, and, in severe cases, spontaneous joint and muscle bleeds similar to those seen in hemophilia.
Although many patients manage occasional bleeding episodes with on-demand treatment, individuals with severe disease often require prophylactic therapy to reduce bleeding frequency and improve quality of life.
Current preventive treatment generally relies on repeated intravenous infusions of von Willebrand factor-containing concentrates, which may need to be administered multiple times each week. These treatment schedules can create a significant burden for patients and caregivers while presenting challenges related to venous access, adherence, and long-term convenience.
A Novel Mechanism of Action
Latarcibart represents a different therapeutic strategy compared with traditional replacement therapies.
Rather than replacing missing or defective von Willebrand factor, the investigational monoclonal antibody targets Protein S, an important regulator of the body’s natural anticoagulation system.
By modulating Protein S activity, latarcibart is designed to enhance hemostasis, the physiological process that controls bleeding following injury.
This mechanism aims to strengthen the body’s ability to form stable blood clots, thereby reducing the frequency and severity of bleeding episodes without directly replacing clotting factors.
Because of this unique mode of action, researchers believe latarcibart may eventually have applications beyond von Willebrand disease, potentially benefiting patients with other inherited or acquired bleeding disorders.
Phase 1/2 Study Overview
The multidose Phase 1/2 clinical trial evaluated both the safety and efficacy of repeated latarcibart administration in patients representing multiple forms of von Willebrand disease.
As of May 5, 2026, complete data were available for all 16 enrolled participants.
Every participant completed the planned multidose treatment regimen, receiving six doses of latarcibart with maintenance injections administered subcutaneously every four weeks.
The study assessed changes in annualized bleeding rates (ABR), breakthrough bleeding, treatment safety, and overall tolerability following repeated administration.
Significant Reductions in Bleeding Episodes
One of the most encouraging findings involved substantial reductions in annualized bleeding rates (ABR) across the study population.
Investigators observed clinically meaningful decreases in bleeding frequency regardless of von Willebrand disease subtype or bleeding category.
The reductions included improvement in several difficult-to-manage bleeding manifestations, including:
- Gastrointestinal bleeding
- Joint bleeding
- Muscle bleeding
- Other clinically significant spontaneous bleeding events
Across all participants and bleeding categories, the median reduction in annualized bleeding rate reached 81 percent, indicating a substantial overall decrease in bleeding burden during treatment.
These improvements suggest that latarcibart may provide broad protection across the diverse clinical presentations associated with von Willebrand disease.
Benefits for Patients Transitioning from Intravenous Prophylaxis
Several participants entered the study while already receiving routine prophylactic treatment with intravenous von Willebrand factor-containing concentrates.
These individuals typically required infusions multiple times each week under existing standards of care.
Among patients transitioning from intravenous prophylaxis to latarcibart, investigators observed additional reductions in bleeding frequency ranging from 75 percent to 100 percent.
These findings suggest that monthly subcutaneous treatment may provide bleeding protection comparable to or potentially better than intensive intravenous replacement therapy for certain patients.
If confirmed in larger Phase 3 studies, this could represent an important advancement by reducing treatment burden while maintaining or improving clinical outcomes.
Improvement Among Patients Without Previous Preventive Therapy
The study also evaluated patients who had not previously received routine intravenous prophylaxis.
Among these participants, seven individuals had historical annualized bleeding rates greater than 12 bleeding events per year, representing patients with particularly high disease burden.
This level of bleeding also serves as one of the key eligibility criteria for enrollment in the ongoing Phase 3 VIVID-6 study.
Within this subgroup, reductions in annualized bleeding rates ranged from 46 percent to 100 percent.
Notably, six of the seven patients achieved reductions exceeding 73 percent, demonstrating consistent clinical benefit among individuals with severe bleeding histories.
These findings indicate that latarcibart may offer meaningful improvements even for patients experiencing frequent spontaneous bleeding before treatment initiation.
Fewer Breakthrough Bleeding Episodes
Researchers also examined the frequency of breakthrough bleeding requiring rescue treatment with von Willebrand factor concentrates.
During treatment with latarcibart, investigators observed approximately an 86 percent reduction in von Willebrand factor-treated breakthrough bleeding episodes.
Among patients who had previously required rescue treatment for breakthrough bleeding, 70 percent experienced no von Willebrand factor-treated breakthrough bleeds while receiving latarcibart.
Reducing breakthrough bleeding is considered an important therapeutic goal because it decreases the need for additional intravenous therapy while helping patients maintain more stable disease control.
Continued Participation in Extension Study
Investigators reported that every participant entering the study with a significant bleeding burden elected to continue receiving latarcibart in the ongoing open-label extension study.
This continued participation will allow researchers to evaluate the durability of bleeding protection, long-term safety, and sustained clinical outcomes over a longer observation period.
Extension studies are particularly valuable in chronic disorders such as von Willebrand disease, where preventive therapies may be administered for many years.
Favorable Safety and Tolerability
Repeated monthly administration of latarcibart was generally well tolerated throughout the study.
Only three treatment-emergent adverse events (TEAEs) considered related to latarcibart were reported.
These included:
- Two Grade 2 headache events occurring in one patient
- One Grade 1 injection-site reaction
Investigators also reported one serious gastrointestinal bleeding event; however, this episode was determined to be unrelated to treatment and occurred in a participant with a documented history of severe, recurrent gastrointestinal bleeding.
Overall, the safety findings support continued evaluation of the investigational therapy in larger clinical trials.
Importantly, no unexpected safety concerns emerged during repeated dosing.
Company Perspective
Pablo J. Cagnoni, M.D., President of Incyte and Global Head of Research and Development, stated that the latest findings reinforce the growing body of evidence supporting latarcibart as a potential new treatment option for patients with von Willebrand disease.
He explained that the multidose data demonstrate the therapy’s ability to provide meaningful bleeding protection across all major forms of VWD while addressing the longstanding need for a more convenient prophylactic treatment.
Cagnoni added that enrollment continues in the pivotal Phase 3 VIVID-6 study as the company works toward establishing a new standard for routine preventive care in patients with the disorder.
Expert Perspective
Allison Wheeler, M.D., MSCI, Associate Professor of Pediatrics at the University of Washington, emphasized the importance of developing more effective and convenient preventive therapies for individuals living with von Willebrand disease.
She noted that many patients continue to struggle with recurrent bleeding despite available treatment options and that the Phase 1/2 study demonstrated clinically meaningful reductions in bleeding across a diverse patient population, including individuals representing all major forms of the disease as well as patients transitioning from intensive intravenous prophylaxis.
Dr. Wheeler also highlighted the favorable safety profile and the convenience of once-monthly subcutaneous dosing, suggesting that the investigational therapy has the potential to substantially reduce treatment burden while providing consistent protection against bleeding.
According to her assessment, these findings establish a strong foundation for the ongoing Phase 3 clinical program and support latarcibart’s potential to become an important new prophylactic treatment option for patients with von Willebrand disease.
The complete Phase 1/2 multidose results presented at ISTH 2026 provide encouraging evidence that latarcibart may offer a meaningful advancement in the management of von Willebrand disease. The investigational monoclonal antibody demonstrated substantial reductions in bleeding frequency across multiple disease subtypes, reduced the need for rescue treatment, and maintained a favorable safety profile with the convenience of once-monthly subcutaneous administration.
As the pivotal Phase 3 VIVID-6 study continues enrollment, researchers will seek to confirm whether these promising early findings translate into consistent long-term benefits in a larger patient population. If successful, latarcibart could become the first once-monthly subcutaneous prophylactic therapy for von Willebrand disease, potentially transforming preventive care by offering patients a more convenient alternative to frequent intravenous replacement therapy while improving protection against recurrent bleeding episodes.
About VGA039 (latarcibart)
VGA039 (latarcibart) is an investigational monoclonal antibody therapy with a novel mechanism of action that targets Protein S, with dual actions promoting platelet attachment and enhancing fibrin deposition to restore hemostasis. Latarcibart has the potential to be a universal prophylactic therapy for numerous bleeding disorders, starting with all types of von Willebrand disease (VWD) and bleeding sites. As a subcutaneously self-administered investigational antibody therapy with a once monthly dosing regimen, latarcibart has the potential to improve bleeding outcomes, convenience, and quality of life for patients.
Latarcibart has received Breakthrough Therapy, Fast Track, orphan drug and rare pediatric disease designations from the U.S. Food and Drug Administration (FDA). Latarcibart has advanced into the Phase 3 VIVID-6 study (NCT07115004), a global single arm cross-over study to investigate safety and efficacy of the subcutaneous administration of latarcibart as prophylaxis for bleeding in patients with every type of VWD, including those with a high disease burden.
Incyte acquired VGA039 (latarcibart) in July 2026 as part of its acquisition of Vega Therapeutics, Inc., a wholly owned subsidiary of Star Therapeutics LLC.
About the VIVID Clinical Program
The VIVID multinational clinical program consists of multiple clinical trials, from Phase 1 to 3, in both a platform multi-phase protocol (VIVID-1-5) and a standalone Phase 3 protocol (VIVID-6) evaluating the safety and efficacy of VGA039 in VWD. The VIVID clinical program is active across 6 continents and designed to support future registrational filings globally.
About von Willebrand Disease
Von Willebrand disease (VWD) is the most common inherited bleeding disorder in which the blood does not clot properly, caused by low or defective von Willebrand factor (VWF). People with VWD may experience excessive bleeding with varying severity and frequency, negatively impacting their daily lives. Current therapies for VWD prophylaxis include factor replacement therapies requiring multiple intravenous (IV) infusions every week. Approximately 135,000 people in the United States have been diagnosed with von Willebrand disease.1
About Incyte®
Incyte is redefining what’s possible in biopharmaceutical innovation. Through deep scientific expertise and a relentless focus on patients, we have built an established portfolio of first-in-class medicines and an extensive portfolio of next-generation medicines across our key franchises: Hematology, Oncology and Inflammation & Autoimmunity.